Due to the current extensive use of methadone and the increased us of its long acting congener 1-alpha-acetylmethadol (LAAM) in maintenance treatment programs for narcotic dependent persons, a thorough understanding of the disposition and biotransformation of these drugs is essential. The major objective of the study are: l) Determine the physiologic disposition and biotransformation of H3 methadone in the monkey in the nontolerant, tolerant and abstient physiologic state; 2) Correlate disposition and metabolism of methadone with tolerance, dependence, abstinence and drug seeking behavior; 3) Conduct plasma, urinary and fecal studies on the pharmacodynamics of methadone in humans following acute and chronic drug administration; 4) Determine the disposition and metabolism of LAAM in the nontolerant, tolerant and abstinent rat, dog and monkey; 5) Correlate disposition and metabolism of LAAM with the pharmacological action of the drug. H3-methadone is currently available in our laboratory, however, the preparation of H3-LAMM is required. Specific methods for the determination of H3-methadone in biological material were developed and will require modification for the estimation of H3-LAAM. Thin-layer, gas-liquid and colum chromatography, as well as NMR, UV and IR spectroscopy and gas-liquid chromatography coupled with mass spectroscopy will be used to ascertain the indentity of the metabolites of these drugs. The monkey self-administration technique will be used to correl ate pharmacological action with disposition and metabolism of these drugs.